Nulojix

"Analysis of three biomarkers in the urine of kidney transplant recipients can diagnose — and even predict — transplant rejection, according to results from a clinical trial sponsored by the National Institute of Allergy and Infect"...

In non-human primate models of renal transplantation,
belatacept monotherapy prolonged graft survival and decreased the production of
anti-donor antibodies, compared to vehicle.

Pharmacodynamics

Belatacept-mediated costimulation blockade results in the
inhibition of cytokine production by T cells required for antigen-specific
antibody production by B cells. In clinical trials, greater reductions in mean
immunoglobulin (IgG, IgM, and IgA) concentrations were observed from baseline
to Month 6 and Month 12 post-transplant in belatacept-treated patients compared
to cyclosporine-treated patients. In an exploratory subset analysis, a trend of
decreasing IgG concentrations with increasing belatacept trough concentrations
was observed at Month 6. Also in this exploratory subset analysis,
belatacept-treated patients with CNS PTLD, CNS infections including PML, other
serious infections, and malignancies were observed to have a higher incidence
of IgG concentrations below the lower limit of the normal range ( < 694 mg/dL)
at Month 6 than those patients who did not experience these adverse events.
This observation was more pronounced with the higher than recommended dose of
belatacept. A similar trend was also observed for cyclosporine-treated patients
with serious infections and malignancies.

However, it is unclear whether any causal relationship
between an IgG concentration below the lower level of normal and these adverse
events exists, as the analysis may have been confounded by other factors (e.g.,
age greater than 60 years, receipt of an extended criteria donor kidney,
exposure to lymphocyte depleting agents) which were also associated with IgG
below the lower level of normal at Month 6 in these trials.

Pharmacokinetics

Table 5 summarizes the pharmacokinetic parameters of
belatacept in healthy adult subjects after a single 10 mg per kg intravenous
infusion; and in kidney transplant patients after the 10 mg per kg intravenous
infusion at Week 12, and after 5 mg per kg intravenous infusion every 4 weeks
at Month 12 post-transplant or later.

* AUC=AUC (INF) after single
dose and AUC (TAU) after multiple dose, where TAU=4 weeks

In healthy subjects, the
pharmacokinetics of belatacept was linear and the exposure to belatacept
increased proportionally after a single intravenous infusion dose of 1 to 20 mg
per kg. The pharmacokinetics of belatacept in de novo kidney transplant
patients and healthy subjects are comparable. Following the recommended
regimen, the mean belatacept serum concentration reached steady-state by Week 8
in the initial phase following transplantation and by Month 6 during the
maintenance phase. Following once monthly intravenous infusion of 10 mg per kg
and 5 mg per kg, there was about 20% and 10% systemic accumulation of
belatacept in kidney transplant patients, respectively.

Based on population
pharmacokinetic analysis of 924 kidney transplant patients up to 1 year
post-transplant, the pharmacokinetics of belatacept were similar at different
time periods post-transplant. In clinical trials, trough concentrations of
belatacept were consistently maintained from Month 6 up to 3 years
post-transplant. Population pharmacokinetic analyses in kidney transplant
patients revealed that there was a trend toward higher clearance of belatacept
with increasing body weight. Age, gender, race, renal function (measured by
calculated glomerular filtration rate [GFR]), hepatic function (measured by
albumin), diabetes, and concomitant dialysis did not affect the clearance of
belatacept.

Drug Interactions

Mycophenolate Mofetil

In a pharmacokinetic substudy of Studies 1 and 2, the
plasma concentrations of MPA were measured in 41 patients who received fixed
MMF doses of 500 to 1500 mg twice daily with either 5 mg per kg of NULOJIX or
cyclosporine. The mean dose-normalized MPA Cmax and AUC0-12 were
approximately 20% and 40% higher, respectively, with NULOJIX coadministration
than with cyclosporine coadministration [see DRUG INTERACTIONS].

Cytochrome P450 Substrates

The potential of NULOJIX to alter the systemic
concentrations of drugs that are CYP450 substrates was investigated in healthy
subjects following administration of a cocktail of probe drugs given concomitantly
with, and at 3 days and at 7 days following a single intravenous 10 mg per kg
dose of NULOJIX. NULOJIX did not alter the pharmacokinetics of drugs that are
substrates of CYP1A2 (caffeine), CYP2C9 (losartan), CYP2D6 (dextromethorphan),
CYP3A (midazolam), and CYP2C19 (omeprazole) [seeDRUG INTERACTIONS].

Animal Toxicology And/Or Pharmacology

Abatacept, a fusion protein that differs from belatacept
by 2 amino acids, binds to the same ligands (CD80/CD86) and blocks T-cell
costimulation like belatacept, but is more active than belatacept in rodents.
Therefore, toxicities identified with abatacept in rodents may be predictive of
adverse effects in humans treated with belatacept.

Studies in rats exposed to abatacept have shown immune
system abnormalities including a low incidence of infections leading to death
(observed in juvenile rats and pregnant rats) as well as autoimmunity of the
thyroid and pancreas (observed in rats exposed in utero, as juveniles or as
adults). Studies of abatacept in adult mice and monkeys, as well as belatacept
in adult monkeys, have not demonstrated similar findings.

The increased susceptibility to opportunistic infections
observed in juvenile rats is likely associated with the exposure to abatacept
before the complete development of memory immune responses. In pregnant rats,
the increased susceptibility to opportunistic infections may be due to the
inherent lapses in immunity that occur in rats during late pregnancy/lactation.
Infections related to NULOJIX have been observed in human clinical trials [see
WARNINGS AND PRECAUTIONS].

Administration of abatacept to rats was associated with a
significant decrease in T-regulatory cells (up to 90%). Deficiency of
T-regulatory cells in humans has been associated with autoimmunity. The
occurrence of autoimmune events across the core clinical trials was infrequent.
However, the possibility that patients administered NULOJIX could develop
autoimmunity (or that fetuses exposed to NULOJIX in utero could develop
autoimmunity) cannot be excluded.

In a 6-month toxicity study with belatacept in cynomolgus
monkeys administered weekly doses up to 50 mg per kg (6 times the MRHD
exposure) and in a 1-year toxicity study with abatacept in adult cynomolgus
monkeys administered weekly doses up to 50 mg per kg, no significant
drug-related toxicities were observed. Reversible pharmacological effects
consisted of minimal transient decreases in serum IgG and minimal to severe
lymphoid depletion of germinal centers in the spleen and/or lymph nodes.

Following 5 doses (10 mg per kg or 50 mg per kg, once a
week for 5 weeks) of systemic administration, belatacept was not detected in
brain tissue of normal healthy cynomolgus monkeys. The number of cells
expressing major histocompatibility complex (MHC) class-II antigens (potential
marker of immune cell activation) in the brain were increased in monkeys
administered belatacept compared to vehicle control. However, distribution of
some other cells expressing CD68, CD20, CD80, and CD86, typically expressed on
MHC class II-positive cells, was not altered and there were no other
histological changes in the brain. The clinical relevance of the findings is
unknown.

Clinical Studies

Prevention Of Organ Rejection In Kidney Transplant
Recipients

The efficacy and safety of NULOJIX in de novo kidney
transplantation were assessed in two open-label, randomized, multicenter,
active-controlled trials (Study 1 and Study 2). These trials evaluated two dose
regimens of NULOJIX, the recommended dosage regimen [see DOSAGE AND
ADMINISTRATION] and a regimen with higher cumulative doses and more
frequent dosing than the recommended dosage regimen, compared to a cyclosporine
control regimen. All treatment groups also received basiliximab induction,
mycophenolate mofetil (MMF), and corticosteroids.

Treatment Regimen

The NULOJIX recommended regimen consisted of a 10 mg per
kg dose administered on Day 1 (the day of transplantation, prior to
implantation), Day 5 (approximately 96 hours after the Day 1 dose), end of
Weeks 2 and 4; then every 4 weeks through Week 12 after transplantation.
Starting at Week 16 after transplantation, NULOJIX was administered at the
maintenance dose of 5 mg per kg every 4 weeks (plus or minus 3 days). NULOJIX
was administered as an intravenous infusion over 30 minutes [seeDOSAGE AND
ADMINISTRATION].

Basiliximab 20 mg was administered intravenously on the
day of transplantation and 4 days later.

The initial dose of MMF was 1 gram twice daily and was
adjusted, as needed based on clinical signs of adverse events or efficacy
failure.

The protocol-specified dosing of corticosteroids in
Studies 1 and 2 at Day 1 was methylprednisolone (as sodium succinate) 500 mg IV
on arrival in the operating room, Day 2, methylprednisolone 250 mg IV, and Day
3, prednisone 100 mg orally. Actual median corticosteroid doses used with the
NULOJIX recommended regimen from Week 1 through Month 6 are summarized in the
table below (Table 6).

Table 6: Actual Corticosteroid* Dosing in Studies 1
and 2

Day of Dosing

Median (Q1-Q3) Daily Dose†,‡

Study 1

Study 2

Week 1

31.7 mg (26.7-50 mg)

30 mg (26.7-50 mg)

Week 2

25 mg (20-30 mg)

25 mg (20-30 mg)

Week 4

20 mg (15-20 mg)

20 mg (15-22.5 mg)

Week 6

15 mg (10-20 mg)

16.7 mg (12.5-20 mg)

Month 6

10 mg (5-10 mg)

10 mg (5-12.5 mg)

* Corticosteroid = prednisone
or prednisolone.
† The protocols allowed for flexibility in determining corticosteroid dose and
rapidity of taper after Day 15. It is not possible to distinguish
corticosteroid doses used to treat acute rejection versus doses used in a
maintenance regimen.
‡ Q1 and Q3 are the 25th and 75th percentiles of daily
corticosteroid doses, respectively.

Study 1 enrolled recipients of
living donor and standard criteria deceased donor organs and Study 2 enrolled
recipients of extended criteria donor organs. Standard criteria donor organs
were defined as organs from a deceased donor with anticipated cold ischemia
time of < 24 hours and not meeting the definition of extended criteria donor
organs. Extended criteria donors were defined as deceased donors with at least
one of the following: (1) donor age ≥ 60
years; (2) donor age ≥ 50 years and other donor comorbidities ( ≥ 2
of the following: stroke, hypertension, serum creatinine > 1.5 mg/dL); (3)
donation of organ after cardiac death; or (4) anticipated cold ischemia time of
the organ of ≥ 24 hours. Study 1
excluded recipients undergoing a first transplant whose current Panel Reactive
Antibodies (PRA) were ≥ 50% and
recipientsundergoing a retransplantation
whose current PRA were ≥ 30%; Study 2
excluded recipients witha current PRA ≥ 30%. Both studies
excluded recipients with HIV, hepatitis C, or evidence of current hepatitis B
infection; recipients with active tuberculosis; and recipients in whom
intravenous access was difficult to obtain.

Efficacy data are presented for
the NULOJIX recommended regimen and cyclosporine regimen in Studies 1 and 2.

The NULOJIX regimen with higher cumulative doses and more
frequent dosing of belatacept was associated with more efficacy failures.
Higher doses and/or more frequent dosing of NULOJIX are not recommended [see DOSAGE
AND ADMINISTRATION, WARNINGS AND PRECAUTIONS, and ADVERSE
REACTIONS].

In Study 1, 666 patients were enrolled, randomized, and
transplanted: 226 to the NULOJIX recommended regimen, 219 to the NULOJIX
regimen with higher cumulative doses and more frequent dosing than recommended,
and 221 to cyclosporine control regimen. The median age was 45 years; 58% of
organs were from living donors; 3% were re-transplanted; 69% of the study
population was male; 61% of patients were white, 8% were
black/African-American, 31% were categorized as of other races; 16% had PRA ≥ 10%;
41% had 4 to 6 HLA mismatches; and 27% had diabetes prior to transplant. The
incidence of delayed graft function was similar in all treatment arms (14% to
18%).

Premature discontinuation from treatment at the end of
the first year occurred in 19% of patients receiving the NULOJIX recommended
regimen and 19% of patients on the cyclosporine regimen. Among the patients who
received the NULOJIX recommended regimen, 10% discontinued due to lack of
efficacy, 5% due to adverse events, and 4% for other reasons. Among the patients
who received the cyclosporine regimen, 9% discontinued due to adverse events,
5% due to lack of efficacy, and 5% for other reasons.

At the end of three years, 25% of patients receiving the
NULOJIX recommended regimen and 34% of patients receiving the cyclosporine
regimen had discontinued from treatment. Among the patients who received the
NULOJIX recommended regimen, 12% discontinued due to lack of efficacy, 7% due
to adverse events, and 6% for other reasons. Among the patients who received
the cyclosporine regimen, 15% discontinued due to adverse events, 8% due to
lack of efficacy, and 11% for other reasons.

Assessment of Efficacy

Table 7 summarizes the results of Study 1 following one
and three years of treatment with the NULOJIX recommended dosage regimen and
the cyclosporine control regimen. Efficacy failure at one year was defined as
the occurrence of biopsy proven acute rejection (BPAR), graft loss, death, or
lost to follow-up. BPAR was defined as histologically confirmed acute rejection
by a central pathologist on a biopsy done for any reason, whether or not
accompanied by clinical signs of rejection. Patient and graft survival was also
assessed separately.

Table 7: Efficacy Outcomes by Years 1 and 3 for Study
1: Recipients of Living and Standard Criteria Deceased Donor Kidneys

Parameter

NULOJIX Recommended Regimen
N=226
n (%)

Cyclosporine (CSA)
N=221
n (%)

NULOJIX-CSA (97.3% CI)

Efficacy Failure by Year 1

49 (21.7)

37 (16.7)

4.9 (-3.3, 13.2)

Components of Efficacy Failure*

Biopsy Proven Acute Rejection

45 (19.9)

23 (10.4)

Graft Loss

5 (2.2)

8 (3.6)

Death

4 (1.8)

7 (3.2)

Lost to follow-up

0

1 (0.5)

Efficacy Failure by Year 3

58 (25.7)

57 (25.8)

-0.1 (-9.3, 9)

Components of Efficacy Failure*

Biopsy Proven Acute Rejection

50 (22.1)

31 (14)

Graft Loss

9 (4)

10 (4.5)

Death

10 (4.4)

15 (6.8)

Lost to follow-up

2 (0.9)

5 (2.3)

Patient and graft survival †

Year 1

218 (96.5)

206 (93.2)

3.2 (-1.5, 8.4)

Year 3

206 (91.2)

192 (86.9)

4.3 (-2.2, 10.8)

* Patients may have experienced
more than one event.
† Patients known to be alive with a functioning graft.

In Study 1, the rate of BPAR at
one year and three years was higher in patients treated with the NULOJIX
recommended regimen than the cyclosporine regimen. Of the patients who
experienced BPAR with NULOJIX, 70% experienced BPAR by Month 3, and 84%
experienced BPAR by Month 6. By three years, recurrent BPAR occurred with
similar frequency across treatment groups ( < 3%). The component of BPAR
determined by biopsy only (subclinical protocol-defined acute rejection) was 5%
in both treatment groups.

Patients treated with the
NULOJIX recommended regimen experienced episodes of BPAR classified as Banff
grade IIb or higher (6% [14/226] at one year and 7% [15/226] at three years)
more frequently compared to patients treated with the cyclosporine regimen (2%
[4/221] at one year and 2% [5/221] at three years). Also, T-cell depleting
therapy was used more frequently to treat episodes of BPAR in NULOJIX-treated
patients (10%; 23/226) compared to cyclosporine­treated patients (2%; 5/221).
At Month 12, the difference in mean calculated glomerular filtration rate (GFR)
between patients with and without history of BPAR was 19 mL/min/1.73 m² among
NULOJIX-treated patients compared to 7 mL/min/1.73 m² among
cyclosporine-treated patients. By three years, 22% (11/50) of NULOJIX-treated
patients with a history of BPAR experienced graft loss and/or death compared to
10% (3/31) of cyclosporine-treated patients with a history of BPAR; at that
time point, 10% (5/50) of NULOJIX-treated patients experienced graft loss and
12% (6/50) of NULOJIX-treated patients had died following an episode of BPAR,
whereas 7% (2/31) of cyclosporine-treated patients experienced graft loss and
7% (2/31) of cyclosporine­treated patients had died following an episode of
BPAR. The overall prevalence of donor-specific antibodies was 5% and 11% for
the NULOJIX recommended regimen and cyclosporine, respectively, up to 36 months
post-transplant.

While the difference in GFR in patients with BPAR versus
those without BPAR was greater in patients treated with NULOJIX than
cyclosporine, the mean GFR following BPAR was similar in NULOJIX (49
mL/min/1.73 m²) and cyclosporine treated patients (43 mL/min/1.73 m²)
at one year. The relationship between BPAR, GFR, and patient and graft survival
is unclear due to the limited number of patients who experienced BPAR,
differences in renal hemodynamics (and, consequently, GFR) across maintenance
immunosuppression regimens, and the high rate of switching treatment regimens
after BPAR.

Assessment of Efficacy in the EBV Seropositive
Subpopulation

In Study 1, approximately 87% of patients were EBV
seropositive prior to transplant. Efficacy results in the EBV seropositive
subpopulation were consistent with those in the total population studied.

By one year, the efficacy failure rate in the EBV seropositive
population was 21% (42/202) in patients treated with the NULOJIX recommended
regimen and 17% (31/184) in patients treated with cyclosporine (difference=4%,
97.3% CI [-4.8, 12.8]). Patient and graft survival was 98% (198/202) in
NULOJIX-treated patients and 92% (170/184) in cyclosporine-treated patients
(difference=5.6%, 97.3% CI [0.8, 10.4]).

By three years, efficacy failure was 25% in both
treatment groups and patient and graft survival was 94% (187/202) in
NULOJIX-treated patients compared with 88% (162/184) in cyclosporine­treated
patients (difference=4.6%, 97.3% CI [-2.1, 11.3]).

Assessment of Glomerular Filtration Rate (GFR)

Glomerular Filtration Rate (GFR) was measured at one and
two years and was calculated using the Modification of Diet in Renal Disease
(MDRD) formula at one, two, and three years after transplantation. As shown in
Table 8, both measured and calculated GFR was higher in patients treated with
the NULOJIX recommended regimen compared to patients treated with the
cyclosporine control regimen at all time points. As shown in Figure 1, the
differences in GFR were apparent in the first month after transplant and were
maintained up to three years (36 months). An analysis of change of calculated
mean GFR between three and 36 months demonstrated an increase of 0.8
mL/min/year (95% CI [-0.2, 1.8]) for NULOJIX-treated patients and a
decrease of 2.2 mL/min/year (95% CI [-3.2, -1.2]) for
cyclosporine-treated patients.

Assessment of Chronic
Allograft Nephropathy (CAN)

The prevalence of chronic
allograftnephropathy (CAN) at one year, as defined by the Banff '97
classification system, was 24% (54/226) in patients treated with the NULOJIX
recommended regimen and in 32% (71/219) of patients treated with the
cyclosporine control regimen. CAN was not evaluated after the first year
following transplantation. The clinical significance of this finding is
unknown.

Study 2: Recipients of Extended
Criteria Donor Kidneys

In Study 2, 543 patients were
enrolled, randomized, and transplanted: 175 to the NULOJIX recommended regimen,
184 to the NULOJIX regimen with higher cumulative doses and more frequent
dosing than recommended, and 184 to the cyclosporine control regimen. The
median age was 58 years; 67% of the study population was male; 75% of patients
were white, 13% were black/African-American, 12% were categorized as of other
races; 3% had PRA ≥ 10%; 53% had 4 to 6
HLA mismatches; and 29% had diabetes prior to transplantation. The incidence of
delayed graft function was similar in all
treatment arms (47% to 49%).

Premature discontinuation from
treatment at the end of the first year occurred in 25% of patients receiving
the NULOJIX recommended regimen and 30% of patients receiving the cyclosporine
control regimen. Among the patients who received the NULOJIX recommended
regimen, 14%discontinued due to adverse events, 9% due to lack of
efficacy, and 2% for other reasons. Among the patients who received the
cyclosporine regimen, 17% discontinued due to adverse events, 7% due to lack of
efficacy, and 6% for other reasons.

At the end of three years, 35% of patients receiving the
NULOJIX recommended regimen and 44% of patients receiving the cyclosporine
regimen had discontinued from treatment. Among the patients who received the
NULOJIX recommended regimen, 20% discontinued due to adverse events, 9% due to
lack of efficacy, and 6% for other reasons. Among the patients who received the
cyclosporine regimen, 25% discontinued due to adverse events, 10% due to lack
of efficacy, and 10% for other reasons.

Assessment of Efficacy

Table 9 summarizes the results of Study 2 following one
and three years of treatment with the NULOJIX recommended dosage regimen and
the cyclosporine control regimen. Efficacy failure at one year was defined as
the occurrence of biopsy proven acute rejection (BPAR), graft loss, death, or
lost to follow-up. BPAR was defined as histologically confirmed acute rejection
by a central pathologist on a biopsy done for any reason, whether or not
accompanied by clinical signs of rejection. Patient and graft survival was also
assessed.

* Patients may have experienced
more than one event.
† Patients known to be alive with a functioning graft.

In Study 2, the rate of BPAR at
one year and three years was similar in patients treated with NULOJIX and
cyclosporine. Of the patients who experienced BPAR with NULOJIX, 62%
experienced BPAR by Month 3, and 76% experienced BPAR by Month 6. By three
years, recurrent BPAR occurred with similar frequency across treatment groups
( < 3%). The component of BPAR determined by biopsy only (subclinical
protocol-defined acute rejection) was 5% in both treatment groups.

A similar proportion of
patients in the NULOJIX recommended regimen group experienced BPAR classified
as Banff grade IIb or higher (5% [9/175] at one year and 6% [10/175] at three
years) compared to patients treated with the cyclosporine regimen (4% [7/184]
at one year and 5% [9/184] at three years). Also, T-cell depleting therapy was
used with similar frequency to treat any episode of BPAR in NULOJIX-treated
patients (5% or 9/175) compared to cyclosporine-treated patients (4% or 7/184).
At Month 12, the difference in mean calculated GFR between patients with and
without a history of BPAR was 10 mL/min/1.73 m² among NULOJIX-treated
patients compared to 14 mL/min/1.73m² among cyclosporine-treated patients.
By three years, 24% (10/42) of NULOJIX-treated patients with a history of BPARexperienced
graft loss and/or death compared to 31% (13/42) of cyclosporine-treated
patients with a history of BPAR; at that time point, 17% (7/42) of
NULOJIX-treated patients experienced graft loss and 14% (6/42) of
NULOJIX-treated patients had died following an episode of BPAR, whereas 19%
(8/42) of cyclosporine-treated patients experienced graft loss and 19% (8/42)
of cyclosporine-treated patients had died following an episode of BPAR. The overall
prevalence of donor-specific antibodies was 6% and 15% for the NULOJIX
recommended regimen and cyclosporine, respectively, up to 36 months
post-transplant.

The mean GFR following BPAR was 36 mL/min/1.73m² in
NULOJIX patients and 24 mL/min/1.73m² in cyclosporine-treated
patients at one year. The relationship between BPAR, GFR, and patient and graft
survival is unclear due to the limited number of patients who experienced BPAR,
differences in renal hemodynamics (and, consequently, GFR) across maintenance
immunosuppression regimens, and the high rate of switching treatment regimens
after BPAR.

Assessment of Efficacy in the EBV Seropositive
Subpopulation

In Study 2, approximately 91% of the patients were EBV
seropositive prior to transplant. Efficacy results in the EBV seropositive
subpopulation were consistent with those in the total population studied.

By one year, the efficacy failure rate in the EBV
seropositive population was 29% (45/156) in patients treated with the NULOJIX
recommended regimen and 28% (47/168) in patients treated with cyclosporine
(difference=0.8%, 97.3% CI [-10.3, 11.9]). Patient and graft survival
rate in the EBV seropositive population was 89% (139/156) in the
NULOJIX-treated patients and 86% (144/168) in cyclosporine-treated patients
(difference=3.4%, 97.3% CI [-4.7, 11.5]).

By three years, efficacy failure was 35% (54/156) in
NULOJIX-treated patients and 36% (61/168) in cyclosporine-treated patients.
Patient and graft survival was 83% (130/156) in NULOJIX-treated patients
compared with 77% (130/168) in cyclosporine-treated patients (difference=5.9%,
97.3% CI [-3.8, 15.6]).

Assessment of Glomerular Filtration Rate (GFR)

Glomerular Filtration Rate (GFR) was measured at one and
two years and was calculated using the Modification of Diet in Renal Disease
(MDRD) formula at one, two, and three years after transplantation. As shown in
Table 10, both measured and calculated GFR was higher in patients treated with
the NULOJIX recommended regimen compared to patients treated with the
cyclosporine control regimen at all time points. As shown in Figure 2, the
differences in GFR were apparent in the first month after transplant and were
maintained up to three years (36 months). An analysis of change of calculated
mean GFR between Month 3 and Month 36 demonstrated a decrease of 0.8
mL/min/year (95% CI [-1.9, 0.3]) for NULOJIX-treated patients and a
decrease of 2.0 mL/min/year (95% CI [-3.1, -0.8]) for
cyclosporine-treated patients.

Assessment of Chronic Allograft
Nephropathy (CAN)

The prevalence of chronic
allograft nephropathy (CAN) at one year, as defined by the Banff '97
classification system, was 46% (80/174) in patients treated with the NULOJIX
recommended regimen and 52% (95/184) of patients treated with the cyclosporine
control regimen. CAN was not evaluated after the first year following
transplantation. The clinical significance of this finding is unknown.

Last reviewed on RxList: 10/14/2014
This monograph has been modified to include the generic and brand name in many instances.